Short and long term influence of phenothiazines on liver peroxisomal fatty acid oxidation in rodents

FEBS Letters

Premereur, N.¹  Vamecq, J.⁴  Van den Branden, C.³  Roels, F.³  Dacremont, G.² 

[1] Pharmacognosy, Phytochemistry and Toxicology, VUB, Laarbeeklaan 103, B-1090 Brussel, Belgium;Kliniek voor Kinderziekten “C. Hooft”, Akademisch Ziekenhuis, RUG, De Pintelaan 185, B-9000 Ghent Germany;Menselijke Anatomie, VUB, Laarbeekkan 103, B-1090 Brussel Belgium;Lab. Chimie Physiologique, UCL & ICP, Avenue Hippocrate 75, B-1200 Brussel Belgium

关键词: Thioridazine;    Chlorpromazine;    Peroxisome;    β-Oxidation;    VLCFA;    T;    thioridazine;    CPZ;    chlorpromazine;    RCA;    residual catalase activity;    VLCFA;    very long chain fatty acid;    LCFA;    long chain fatty acid;   

DOI  :  10.1016/0014-5793(87)80184-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Evidence is given that phenothiazines depress hepatic peroxisomal fatty acid oxidation in vivo. After oral administration to rats thioridazine and chlorpromazine inhibit peroxisomal β-oxidation, evaluated by H₂O₂ production, during 2 weeks. In mice, this effect could not be demonstrated. However, in both species VLCFA are increased after short and long term drug administration. Electron microscopy reveals the presence of membranous structures in liver cytoplasm or lysosomes. The inhibition by thioridazine of peroxisomal β-oxidation does not lead to hepatic peroxisome proliferation. The activities of enzymes related to fatty acid breakdown are not increased and liver peroxisomes are microscopically normal.

【 授权许可】

Unknown